- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT03028142
The Effects of RPL554 in Addition to Tiotropium in COPD Patients
Aperçu de l'étude
Statut
Les conditions
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- Male or female aged between 40 and 75 years inclusive, at the time of informed consent.
If male: must agree to meet the following from the first dose up to 1 month after the last dose of study treatment:
- Not donate sperm
- Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second highly effective form of contraception must also be used
If female: either be:
Of non-childbearing potential defined as being:
- Either: post-menopausal (being spontaneously amenorrhoeic for at least 1 year with an appropriate clinical profile [e.g. age appropriate, history of vasomotor symptoms]
- Or: permanently sterilised e.g. tubal occlusion, hysterectomy, bilateral oophorectomy, bilateral salpingectomy
- Of childbearing potential and agreeing to use a highly effective method of contraception until completion of the end of study visit.
Have a 12-lead ECG recording at screening and randomisation (pre-dose in Treatment Period 1) showing the following:
- Heart rate between 45 and 90 beats per minute (bpm)
- QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males and ≤470 ms for females
- QRS interval ≤120 msec
- No clinically significant abnormalities (as judged by the Investigator) including morphology (e.g. left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities)
Have a screening Holter report with a minimum of 18 hours recording that is able to be evaluated for rhythm analysis which shows no abnormality which indicates a significant impairment of patient safety or which may significantly impairs interpretation in the opinion of the Investigator including:
- Significant arrhythmias including atrial flutter, atrial fibrillation, ventricular tachycardia
- Any symptomatic arrhythmia (except isolated extra systoles)
- Any sustained second or third degree heart block
- Capable of complying with all study restrictions and procedures including ability to use the study nebuliser and HandiHaler® DPI correctly.
- Body mass index (BMI) between 18 and 33 kg/m2 (inclusive) with a minimum weight of 45 kg.
- COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to screening.
Post-bronchodilator (four puffs of salbutamol) spirometry at screening:
- Post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of ≤0.70
- Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
- Demonstrates ≥150 mL increase from pre-bronchodilator FEV1
- Clinically stable COPD in the 4 weeks prior to screening and randomisation (pre-dose in Treatment Period 1).
- A chest X-ray (post-anterior) at screening, or in the 12 months prior to screening showing no abnormalities, which are both clinically significant and unrelated to COPD.
- Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
- Smoking history of ≥10 pack years.
- Capable of withdrawing from long acting bronchodilators for the duration of the study, and short acting bronchodilators for 8 hours prior to spirometry.
Exclusion Criteria:
- A history of life-threatening COPD exacerbation including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral steroids, or lower respiratory tract infection requiring antibiotics, in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- A history of one or more hospitalisations for COPD in the 12 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- Lactation (female patients only).
- Positive urine or serum pregnancy test at screening, or a positive urine pregnancy test prior to randomisation (female patients of childbearing potential only).
- Prior exposure to RPL554 or known hypersensitivity to RPL554 or its components.
- Intolerance or hypersensitivity to tiotropium.
- Evidence of cor pulmonale.
- Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnoea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Previous lung resection or lung reduction surgery.
- Use of oral COPD medications (e.g. oral steroids, theophylline and romifulast) in the 3 months prior to screening or randomisation (pre-dose in Treatment Period 1).
- History of, or reason to believe, a patient has drug or alcohol abuse within the past 3 years.
- Inability to perform technically acceptable spirometry or whole body plethysmography (at screening or randomisation [pre dose in Treatment Period 1])
- Received an experimental drug within 30 days or five half lives, whichever is longer.
- Patients with a history of chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, haematological, urological, immunological, or ophthalmic diseases that the Investigator believes are clinically significant.
- Documented cardiovascular disease: arrhythmias, angina, recent or suspected myocardial infarction, congestive heart failure, a history of unstable, or uncontrolled hypertension, or has been diagnosed with hypertension in the 3 months prior to screening or randomisation.
- Concurrent use of non-cardioselective oral beta-blockers.
- Has had major surgery, (requiring general anaesthesia) in the 6 weeks prior to screening or randomisation (pre-dose in Treatment Period 1), or will not have fully recovered from surgery, or planned surgery through the end of the study.
- A disclosed history or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
- Requires oxygen therapy, even on an occasional basis.
- Clinically significant prostatic hyperplasia (judged by the Investigator) or bladder-neck obstruction or with narrow-angle glaucoma.
- Any other reason that the Investigator considers makes the patient unsuitable to participate.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Lower Dose Nebulised Treatment
1.5 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
|
Expérimental: Higher Dose Nebulised Treatment
6 mg nebulised RPL554 twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
|
Comparateur placebo: Placebo
Nebulised RPL554 matched placebo twice daily plus 10 mcg tiotropium DPI once daily for 3 days
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Peak Forced Expired Volume in 1 Second (FEV1) on the Third Day of Dosing
Délai: Day 3
|
Peak forced expired volume in 1 second (FEV1) over 4 hours on the third day of dosing
|
Day 3
|
Average FEV1 Over 12 Hours on the Third Day of Dosing
Délai: Day 3
|
Average FEV1 area under the curve (AUC) over 12 hours on the third day of dosing
|
Day 3
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Peak FEV1 on Day 1
Délai: Day 1
|
Peak FEV1 over 4 hours on Day 1
|
Day 1
|
Average FEV1 Over 12 Hours on Day 1
Délai: Day 1
|
Average FEV1 AUC over 12 hours on Day 1
|
Day 1
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Maladies pulmonaires
- Maladies pulmonaires obstructives
- Maladie pulmonaire obstructive chronique
- Effets physiologiques des médicaments
- Agents neurotransmetteurs
- Mécanismes moléculaires de l'action pharmacologique
- Parasympatholytiques
- Agents autonomes
- Agents du système nerveux périphérique
- Antagonistes cholinergiques
- Agents cholinergiques
- Agents bronchodilatateurs
- Agents anti-asthmatiques
- Agents du système respiratoire
- Bromure de tiotropium
Autres numéros d'identification d'étude
- RPL554-CO-202
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
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